Identification of Potential WSB1 Inhibitors by AlphaFold Modeling, Virtual Screening, and Molecular Dynamics Simulation Studies

Ye Weng; Chenghao Pan; Zheyuan Shen; Sikang Chen; Lei Xu; Xiaowu Dong; Jing Chen

doi:10.1155/2022/4629392

Identification of Potential WSB1 Inhibitors by AlphaFold Modeling, Virtual Screening, and Molecular Dynamics Simulation Studies

Evid Based Complement Alternat Med. 2022 May 13:2022:4629392. doi: 10.1155/2022/4629392. eCollection 2022.

Authors

Ye Weng¹, Chenghao Pan², Zheyuan Shen², Sikang Chen², Lei Xu³, Xiaowu Dong², Jing Chen⁴

Affiliations

¹ The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China.
² School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
³ Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310018, China.
⁴ Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, Jiangsu, China.

Abstract

WD40 repeat and SOCS box containing 1 (WSB1) consists of seven WD40 repeat structural domains at the N-terminal end and one SOCS box structural domain at the C-terminal end. WSB1 promotes cancer progression by affecting the Von Hippel-Lindau tumor suppressor protein (pVHL) and upregulating hypoxia inducible factor-1α (HIF-1α) target gene expression. However, the crystal structure of WSB1 has not been reported, which is not beneficial to the research on WSB1 inhibitors. Therefore, we focused on specific small molecule inhibitors of WSB1. This study applied virtual screening and molecular dynamics simulations; finally, 20 compounds were obtained. Among them, compound G490-0341 showed the best stable structure and was a promising composite for further development of WSB1 inhibitors.